Radiation makes cells select the form of death dependent on external or internal exposure: apoptosis or pyroptosis.

Internal radiation exposure from neutron-induced radioisotopes environmentally activated following atomic bombing or nuclear accidents should be considered for a complete picture of pathologic effects on survivors. Acute and localized high dose radiation exposure from hot particles taken into the body must induce cell death and severe damage to tissues, whether they are proliferating or not. However, very little the cellular and molecular mechanisms underlying this internal radiation pathology has been investigated. Male Wistar rats were internally exposed to 56MnO2 powder by inhalation. Small intestine samples were investigated by histological staining at acute phase (6 h, 3 days and 14 days) and late phase (2, 6 and 8 months) after the exposure. Histological location and chemical properties of the hot particles embedded in small intestinal tissues were analyzed by synchrotron radiation-X-ray fluorescence-X-ray absorption near-edge structure (SR-XRF-XANES). Hot particles located in the intestinal cavity were identified as accumulations of Mn and iron. Pathological changes showed evidence of crypt shortening, massive cell death at the position of stem cell zone, including apoptosis and pyroptosis from 6 h through 8 months in the internal exposed rats.

Pathological observation of the effects of exposure to radioactive microparticles on experimental animals.

Internal radiation exposure from neutron-induced radioisotopes that were environmentally activated following an atomic bombing or nuclear accident should be considered for a complete picture of the pathologic effects on survivors. Inhaled hot particles expose neighboring tissues to very high doses of particle beams, which can cause local tissue damage. Experimentally, a few µm of 55MnO2 powder was irradiated with neutrons at a nuclear reactor in order to generate 56MnO2 that emits ß-rays. Rats were irradiated via inhalation. Pathological changes in various rat tissues were examined. In addition, the 56Mn ß energy spectrum around the particles was calculated to determine the local dose rate and the cumulative dose. This review focuses on our latest pathological findings in lungs with internal radiation injury and discusses the pathological changes of early event damage caused by localized, very high-dose internal radiation exposure, including apoptosis, elastin stigma, emphysema, hemorrhage and severe inflammation. The pathological findings of lung tissue due to internal radiation exposure of 0.1 Gy were severe, with no pathological changes observed due to external exposure to γ radiation at a dose of 2.0 Gy. Therefore, it is suggested that new pathological analysis methods for internal exposure due to radioactive microparticles are required.

Impact of Local High Doses of Radiation by Neutron Activated Mn Dioxide Powder in Rat Lungs: Protracted Pathologic Damage Initiated by Internal Exposure.

Internal radiation exposure from neutron-induced radioisotopes environmentally activated following atomic bombing or nuclear accidents should be considered for a complete picture of pathologic effects on survivors. Inhaled hot particles expose neighboring tissues to locally ultra-high doses of ß-rays and can cause pathologic damage. 55MnO2 powder was activated by a nuclear reactor to make 56MnO2 which emits ß-rays. Internal exposures were compared with external γ-rays. Male Wistar rats were administered activated powder by inhalation. Lung samples were observed by histological staining at six hours, three days, 14 days, two months, six months and eight months after the exposure. Synchrotron radiation - X-ray fluorescence - X-ray absorption near-edge structure (SR-XRF-XANES) was utilized for the chemical analysis of the activated 56Mn embedded in lung tissues. 56Mn beta energy spectrum around the particles was calculated to assess the local dose rate and accumulated dose. Hot particles located in the bronchiole and in damaged alveolar tissue were identified as accumulations of Mn and iron. Histological changes showed evidence of emphysema, hemorrhage and severe inflammation from six hours through eight months. Apoptosis was observed in the bronchiole epithelium. Our study shows early event damage from the locally ultra-high internal dose leads to pathogenesis. The trigger of emphysema and hemorrhage was likely early event damage to blood vessels integral to alveolar walls.

Statistical resolutions for large variabilities in hair mineral analysis.

Measuring biomaterials is usually subject to error. Measurement errors are classified into either random errors or biases. Random errors can be well controlled using appropriate statistical methods. But, biases due to unknown, unobserved, or temporary causes, may lead to biased conclusions. This study describes a verification method to examine whether measurement errors are random or not and to determine efficient statistical methods. A number of studies have dealt with associations between hair minerals and exposures such as health, dietary or environmental conditions. Most review papers, however, emphasize the necessity for validation of hair mineral measurements, since large variations can cause highly variable results. To address these issues, we answer the following questions: How can we ascertain the reliability of measurements?How can we assess and control the variability of measurements?How do we efficiently determine associations between hair minerals and exposures?How can we concisely present the reference values? Since hair minerals all have distinctive natures, it would be unproductive to examine each mineral individually to find significant and consistent answers that apply to all minerals. To surmount this difficulty, we used one simple model for all minerals to explore quantitative answers. Hair mineral measurements of six-year-old children were analyzed based on the statistical model. The analysis verified that most of the measurements were reliable, and their inter-individual variations followed two-parameter distributions. These results allow for sophisticated study designs and efficient statistical methods to examine the effects of various kinds of exposures on hair minerals.

The Knowledge and Awareness for Radiocesium Food Monitoring after the Fukushima Daiichi Nuclear Accident in Nihonmatsu City, Fukushima Prefecture.

On 11 March 2011, Japan experienced a massive earthquake and tsunami that triggered the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, resulting in the release of large amounts of cesium-134 and -137 into the atmosphere. In addition to the food radioactivity control in the markets throughout the country, radiocesium concentrations in locally grown foods were voluntarily inspected and the results were shown to the residents by the local government to raise their awareness of the internal radiation contamination risk from low knowledge in Nihonmatsu City, Fukushima Prefecture. In this longitudinal study, local food products for in-home consumption were evaluated by seven different food radioactivity measuring devices in Nihonmatsu City from 2011⁻2017. Radiocesium was detected in local foods in Nihonmatsu City even six years after the FDNPP accident. The highest number of products tested was in 2012, with the number steadily decreasing thereafter. Most foods had contamination levels that were within the provisional regulation limits. As edible wild plants and mushrooms continue to possess high radiocesium concentrations, new trends in radioactivity in foods like seeds were discovered. This study highlights that the increased risk of radiation exposure could possibly be due to declining radiation awareness among citizens and food distributors. We recommend the continuation of food monitoring procedures at various points in the food processing line under the responsibility of the government to raise awareness for the reduction of future risks of internal exposure.

Autoradiographic analysis of internal plutonium radiation exposure in Nagasaki atomic bomb victims.

BACKGROUND: Radiation doses received by Hiroshima and Nagasaki atomic bomb survivors has been evaluated from data related only to external exposure because there was no reliable evidence for internal exposure in atomic bomb victims. However, we assumed that the contribution of internal exposure cannot be ruled out. METHODS: Autoradiography was carried out with the 70-year old paraffin-embedded specimens taken from Nagasaki atomic bomb victims who died within 5 months after the bombing. After exposure to photo emulsion for 6 months alpha-tracks were revealed in the specimens. We confirmed the alpha-tracks were emitted from deposited plutonium (Pu) in reference to the track length of the 8.787 MeV alpha-particle of thorium series from Polonium-212. Radioactivity concentration of Pu was obtained by counting alpha-tracks. The absorbed dose of each cell nucleus penetrated by an alpha-particle was estimated by calculating the absorbed energy from the particle. RESULTS: Using old paraffin embedded sections processed about 70 years ago, we demonstrated for the first time that conditions in the aftermath of the bombing led to internal exposure to alpha-particles emitted from Pu, the fissile material of the Nagasaki atomic bomb. Dose rate of internal exposure was higher in the victims exposed outdoors than those indoors. Radioactivity concentration was relatively uniform among organs examined in a victim. CONCLUSION: Pu was deposited in the bodies of the Nagasaki A-bomb victims presumably via various routes. Organ dose from Pu of the Nagasaki A-bomb victims studied was during their surviving period, which is lower compared with external exposure. However, the impact to the individual cell nucleus by a single alpha-particle might not be negligible, It would be meaningful; to analyze the relationship of the impact of internal exposure at the cellular level and organ dose. The 70-year old pathological specimens utilized in our study are an invaluable source for understanding internal radiation exposure and are crucial in elucidating experimentally unreproducible phenomena.

Internal exposure to neutron-activated 56Mn dioxide powder in Wistar rats: part 1: dosimetry.

There were two sources of ionizing irradiation after the atomic bombings of Hiroshima and Nagasaki: (1) initial gamma-neutron irradiation at the moment of detonation and (2) residual radioactivity. Residual radioactivity consisted of two components: radioactive fallout containing fission products, including radioactive fissile materials from nuclear device, and neutron-activated radioisotopes from materials on the ground. The dosimetry systems DS86 and DS02 were mainly devoted to the assessment of initial radiation exposure to neutrons and gamma rays, while only brief considerations were given for the estimation of doses caused by residual radiation exposure. Currently, estimation of internal exposure of atomic bomb survivors due to dispersed radioactivity and neutron-activated radioisotopes from materials on the ground is a matter of some interest, in Japan. The main neutron-activated radionuclides in soil dust were 24Na, 28Al, 31Si, 32P, 38Cl, 42K, 45Ca, 46Sc, 56Mn, 59Fe, 60Co, and 134Cs. The radionuclide 56Mn (T 1/2 = 2.58 h) is known as one of the dominant beta- and gamma emitters during the first few hours after neutron irradiation of soil and other materials on ground, dispersed in the form of dust after a nuclear explosion in the atmosphere. To investigate the peculiarities of biological effects of internal exposure to 56Mn in comparison with external gamma irradiation, a dedicated experiment with Wistar rats exposed to neutron-activated 56Mn dioxide powder was performed recently by Shichijo and coworkers. The dosimetry required for this experiment is described here. Assessment of internal radiation doses was performed on the basis of measured 56Mn activity in the organs and tissues of the rats and of absorbed fractions of internal exposure to photons and electrons calculated with the MCNP-4C Monte Carlo using a mathematical rat phantom. The first results of this international multicenter study show that the internal irradiation due to incorporated 56Mn powder is highly inhomogeneous, and that the most irradiated organs of the experimental animals are: large intestine, small intestine, stomach, and lungs. Accumulated absorbed organ doses were 1.65, 1.33, 0.24, 0.10 Gy for large intestine, small intestine, stomach, and lungs, respectively. Other organs were irradiated at lower dose levels. These results will be useful for interpretation of the biological effects of internal exposure of experimental rats to powdered 56Mn as observed by Shichijo and coworkers.

[Measures against Radiation Exposure Due to Large-Scale Nuclear Accident in Distant Place--Radioactive Materials in Nagasaki from Fukushima Daiichi Nuclear Power Plant].

OBJECTIVE: To investigate human health effects of radiation exposure due to possible future nuclear accidents in distant places and other various findings of analysis of the radioactive materials contaminating the atmosphere of Nagasaki due to the Fukushima Daiichi Nuclear Power Plant accident. METHODS: The concentrations of radioactive materials in aerosols in the atmosphere of Nagasaki were measured using a germanium semiconductor detector from March 2011 to March 2013. Internal exposure dose was calculated in accordance with ICRP Publ. 72. Air trajectories were analyzed using NOAA and METEX web-based systems. RESULTS: (134)Cs and (137)Cs were repeatedly detected. The air trajectory analysis showed that (134)Cs and (137)Cs flew directly from the Fukushima Daiichi Nuclear Power Plant from March to April 2011. However, the direct air trajectories were rarely detected after this period even when (134)Cs and (137)Cs were detected after this period. The activity ratios ((134)Cs/(137)Cs) of almost all the samples converted to those in March 2011 were about unity. This strongly suggests that the (134)Cs and (137)Cs detected mainly originated from the Fukushima Daiichi Nuclear Power Plant accident in March 2011. Although the (134)Cs and (137)Cs concentrations per air volume were very low and the human health effects of internal exposure via inhalation is expected to be negligible, the specific activities (concentrations per aerosol mass) were relatively high. CONCLUSION: It was found that possible future nuclear accidents may cause severe radioactive contaminations, which may require radiation exposure control of farm goods to more than 1000 km from places of nuclear accidents.

Ingestion of radioactively contaminated diets for two generations in the pale grass blue butterfly.

BACKGROUND: The release of radioactive materials due to the Fukushima nuclear accident has raised concern regarding the biological impacts of ingesting radioactively contaminated diets on organisms. We previously performed an internal exposure experiment in which contaminated leaves collected from polluted areas were fed to larvae of the pale grass blue butterfly, Zizeeria maha, from Okinawa, which is one of the least polluted localities in Japan. Using the same experimental system, in the present study, we further examined the effects of low-level-contaminated diets on this butterfly. Leaves were collected from two localities in Tohoku (Motomiya (161 Bq/kg) and Koriyama (117 Bq/kg)); two in Kanto (Kashiwa (47.6 Bq/kg) and Musashino (6.4 Bq/kg)); one in Tokai (Atami (2.5 Bq/kg)); and from Okinawa (0.2 Bq/kg). In addition to the effects on the first generation, we examined the possible transgenerational effects of the diets on the next generation. RESULTS: In the first generation, the Tohoku groups showed higher rates of mortality and abnormalities and a smaller forewing size than the Okinawa group. The mortality rates were largely dependent on the ingested dose of caesium. The survival rates of the Kanto-Tokai groups were greater than 80%, but the rates in the Tohoku groups were much lower. In the next generation, the survival rates in the Tohoku groups were below 20%, whereas those of the Okinawa groups were above 70%. The survival rates in the second generation were independent of the locality of the leaves ingested by the first generation, indicating that the diet in the second generation was the determinant of their survival. Moreover, a smaller forewing size was observed in the Tohoku groups in the second generation. However, the forewing size was inversely correlated with the cumulative caesium dose ingested throughout the first and second generations, indicating that the diet in the first generation also influenced the forewing size of the second generation. CONCLUSIONS: Biological effects are detectable under a low ingested dose of radioactivity from a contaminated diet. The effects are transgenerational but can be overcome by ingesting a non-contaminated diet, suggesting that at least some of the observed effects are attributable to non-genetic physiological changes.

Cohort study for prevention of atopic dermatitis using hair mineral contents.

We undertook a cohort study to determine the association between hair mineral content and the onset of atopic dermatitis (AD) in infants. Eight hundred and thirty-four mother-infant pairs, who donated hair samples during one and ten-month health checkups, had their samples analyzed by proton induced X-ray emission (PIXE) for 32 mineral concentrations, and these mineral concentration data together with their AD family history were statistically examined for any relationships between them. Results indicated that of all minerals, only selenium (Se) and strontium (Sr) showed statistically significant associations for infants, while the same two elements were only marginally significant for mothers. Se deficiency in either infant or mother increased the AD risk. A Sr deficiency in infants increased AD risk, while the same deficiency in mothers decreased the risk. To predict the probability of AD development using this data, we performed logistic regression analysis, which provided a sensitivity of 65.9%, a specificity of 70.5%, a positive predictive value (PPV) of 10.3%, a negative predictive value (NPV) of 97.6% and a relative risk (RR) of 4.2, all far better than any corresponding figures explicitly mentioned in previously published papers.

Induction of micronuclei in germinating onion seed root tip cells irradiated with high energy heavy ions.

Effects of high LET charged particles on a perfect in-vivo system are an essential theme for the study of the biological effects of radiation. Germinating onion seeds are independent complete organisms and the radiation induced micronuclei in the root chip cells can be examined quantitatively and theoretically. We irradiated with three types of high energy accelerated heavy ions germinating onion seeds using a synchrotron and observed micronuclei in the root tip cells. Micronuclei induction showed characteristic dose responses of an upward convex bell shape and a steep rise near zero doses for all types of the ions. The bell curve dose responses, however, could be explained by a simple mathematical model. A parameter in the model which indicates micronuclei induction frequency and another parameter which indicates induction frequency of lethal damages (or damages delaying cell divisions) per heavy ion track were both proportional to square of the LET. Because we suspected by-stander effect concerning the dose responses rising steeply near zero doses and tapering off for higher doses, we tested acute irradiation to remove time of information transmittance between cells using a single spill (about 0.3 s) of the synchrotron beam. No difference was detected between normal multiple spill irradiations and single spill.

Long incubation period for the induction of cancer by thorotrast is attributed to the uneven irradiation of liver cells at the microscopic level.

Irradiation from internally deposited radionuclides induces malignant tumors. Ingested long-lived radionuclides accumulate in specific organs that are irradiated throughout life. To elucidate why the development of malignant tumors requires long-term internal exposure, of the order of decades, despite the fact that irradiation is continuous over this period, we analyzed intrahepatic cholangiocarcinoma in Thorotrast patients (Th-ICC). Autoradiography showed that the density of alpha-particle tracks was 50 times more concentrated than would be expected if Thorotrast were evenly distributed throughout the liver. The age-incidence curves revealed that while the incidence of hepatobiliary cancer in Japan increased in proportion to the 7th power of age, that of Th-ICC increased to the 6th power. Internal radiation significantly increased the randomness of hepatocyte distribution but not the density. Three major factors are considered to be responsible for the long incubation time: the uneven distribution of radionuclides, the limited range of radiation, and the movement of tumor precursor cells. Target cells susceptible to malignant transformation may undergo one event and may then migrate outside of the range of alpha particles, thereby avoiding immediate induction of successive additional events that would lead to cell death or neoplastic changes.

Development, beam characterization and chromosomal effectiveness of X-rays of RBC characteristic X-ray generator.

A characteristic hot-filament type X-ray generator was constructed for irradiation of cultured cells. The source provides copper K, iron K, chromium K, molybdenum L, aluminium K and carbon K shell characteristic X-rays. When cultured mouse m5S cells were irradiated and frequencies of dicentrics were fitted to a linear-quadratic model, Y = alphaD + betaD2, the chromosomal effectiveness was not a simple function of photon energy. The alpha-terms increased with the decrease of the photon energy and then decreased with further decrease of the energy with an inflection point at around 10 keV. The beta-terms stayed constant for the photon energy down to 10 keV and then increased with further decrease of energy. Below 10 keV, the relative biological effectiveness (RBE) at low doses was proportional to the photon energy, which contrasted to that for high energy X- or gamma-rays where the RBE was inversely related with the photon energy. The reversion of the energy dependency occurred at around 1-2 Gy, where the RBE of soft X-rays was insensitive to X-ray energy. The reversion of energy-RBE relation at a moderate dose may shed light on the controversy on energy dependency of RBE of ultrasoft X-rays in cell survival experiments.

Measuring the external exposure dose in the contaminated area near the Chernobyl nuclear power station using the thermoluminescence of quartz in bricks.

We collected bricks from buildings in the heavily contaminated evacuated area of Belarus in a 30-km zone around the Chernobyl nuclear power station and the Gomel-Bryansk area of 150-250 km from Chernobyl and estimated the cumulative radiation dose caused by the reactor accident by measuring the thermoluminescence (TL) of the bricks. The annual dose at each location was measured using glass dosimeters and thermoluminescence dosimeters (TLD). The dose rate was measured using an energy-compensated NaI scintillation survey meter. The soil contamination near the location of each brick was measured using a germanium semiconductor detector. The main purpose of the project was to extrapolate the relation between the cumulative external dose and the present dose rate or contamination level to the lower contaminated areas. The results of the glass dosimeter, TLD, and survey meter determinations were almost identical. For a determination of the annual dose higher than 10 mGy y(-1), the cumulative dose by TL (TL dose) was roughly proportional to the annual dose and about 1.5 times larger than the cumulative dose calculated from the annual dose and 137Cs half life. The difference is expected due to the contribution of short-lived nuclides immediately after the accident or localized heavy contamination of the ground surface with 137Cs that migrated afterwards. For annual dose smaller than 10 mGy y(-1), the proportionality was not observed and most of the locations facing indoors showed TL doses very much larger than that expected from the proportionality. The cumulative dose outdoors by TL was also roughly proportional to the regional 137Cs contamination level and the proportional constant is about 10(-1) mGy per GBq km(-2), and is about 250 times larger than the present annual internal dose derived from published results. The correlation between the present dose rate where the brick was sampled and the average 137Cs concentration in the ground soil near the point is not clear, possibly because of the large spatial fluctuation in the 137Cs concentration in the soil.